Project Summary Pulmonary hypertension is a disease that occurs most frequently as complicating comorbidity of very common disease in the western world including COPD, Heart Failure and Blood Clots in the lung. Its presence alone or in combination with other conditions leads to significant morbidity and mortality. Medications developed successfully for Group I disease have not shown as much utility in Group II (Due to left heart disease) and Group III (due to lung disease) PH. It has been proposed that this may be due to an inability to identify subtypes of PH that respond to this type of treatment. Additionally, non-invasive screening and early detection remain challenging. Radiologists have been making observations of the loss of distal vasculature (pruning), increase vascular ?tortuosity?, and proximal dilation of the pulmonary vasculature. Algorithms developed and implemented by Dr. Rahaghi and the Applied Chest Imaging Laboratory (ACIL) group permit the 3D reconstruction and quantification of the structure of pulmonary vasculature using CT scans. Dr. Rahaghi has already deployed these algorithms in multiple cohorts generating publications and preliminary data. In his first aim, Dr. Rahaghi will explore the differences in the structure of the pulmonary vasculature between different groups of pulmonary hypertension and subjects without pulmonary hypertension and relate these findings to disease severity. In the second aim, he will study the extent to which pulmonary vascular structure can predict right ventricular dysfunction, a key event in the progression of disease that is predictive of poor outcome and signals the need for more aggressive treatment. In the third aim, he will study pulmonary vascular structure and its relationship to pulmonary vascular mechanics during exercise. This work will be performed at the Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital, a core teaching hospital of Harvard Medical School, under the supervision of two mentors, Dr. Washko who is an expert in clinical lung imaging and Dr. Waxman who is an expert in clinical pulmonary hypertension. The site is one of six in the nation chosen as part of the PVDOMICS project which is NIH funded effort to subtype pulmonary hypertension. Dr. Rahaghi's team includes members of the Applied Chest Imaging Laboratory which includes a team of mathematicians and computer scientists who have a decade long collaboration in creating computer algorithms for image-processing of the lung. Dr. Rahaghi has a life-long dedication to becoming a physician-scientist with a focus on quantitative sciences and their applications to medicine. He has a background in physics and a Ph.D. in Bioengineering as part of a NIH sponsored medical-scientist training program. He plans to use the knowledge he gains by interacting with patients who have pulmonary hypertension and his knowledge of engineering and study design to improve care and outcomes in PH.